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Neutrophils in the lung: “the first responders”

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Abstract

Neutrophils, constituting the first line of defense, perform vital functions during immune surveillance. A key feature that assists in their prompt response to an inflammatory signal is rapid migration to the affected site. They are normally short-lived but can be activated to live longer under the influence of an inflammatory stimulus. They can, thereby, release their toxic granule contents that are differentially housed inside the cytoplasm. Although these events are well characterized in the peripheral circulation, we are still far from fully understanding their recruitment in lungs. Lungs are a reservoir of neutrophils under steady-state. In the event of an infection or injury, they promptly activate and recruit to the alveolar compartment as well as the airways. Lung intravital microscopy has revealed that neutrophils display novel features during steady- and activated-state highlighting key differences in the lung vasculature compared to peripheral sites. This review will discuss neutrophil biology in lung inflammation and will highlight the role of angiostatin, an anti-angiogenic molecule, as well as vitronectin, an acute phase secreted plasma protein, in lung neutrophil recruitment.

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References

  • Andonegui G, Bonder CS, Green F, Mullaly SC, Zbytnuik L, Raharjo E, Kubes P (2003) Endothelium-derived toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs. J Clin Investig 111:1011–1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andonegui G, Kerfoot SM, McNagny K, Ebbert KVJ, Patel KD, Kubes P (2005) Platelets express functional toll-like receptor-4. Blood 106:2417–2423

    Article  CAS  PubMed  Google Scholar 

  • Andonegui G, Trevani AS, López DH, Raiden S, Giordano M, Geffner JR (1997) Inhibition of human neutrophil apoptosis by platelets. J Immunol 158:3372–3377

    CAS  PubMed  Google Scholar 

  • Aulakh GK, Balachandran Y, Liu L, Singh B (2013) Angiostatin inhibits activation and migration of neutrophils. Cell Tissue Res 355:375–396

  • Aulakh GK, Suri SS, Singh B (2014) Angiostatin inhibits acute lung injury in a mouse model. Am J Physiol Lung Cell Mol Physiol 306:L58–L68

    Article  CAS  PubMed  Google Scholar 

  • Bae HB, Tadie JM, Jiang S, Park DW, Bell CP, Thompson LC, Peterson CB, Thannickal VJ, Abraham E, Zmijewski JW (2013) Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages. J Immunol (Baltimore, Md : 1950) 190:2273–2281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beerepoot LV, Witteveen EO, Groenewegen G, Fogler WE, Sim BK, Sidor C, Zonnenberg BA, Schramel F, Gebbink MF, Voest EE (2003) Recombinant human angiostatin by twice-daily subcutaneous injection in advanced cancer: a pharmacokinetic and long-term safety study. Clin Cancer Res 9:4025–4033

    CAS  PubMed  Google Scholar 

  • Bhattacharya J, Matthay MA (2013) Regulation and repair of the alveolar-capillary barrier in acute lung injury. Annu Rev Physiol 75:593–615

    Article  CAS  PubMed  Google Scholar 

  • Bickenbach J, Dembinski R, Czaplik M, Meissner S, Tabuchi A, Mertens M, Knels L, Schroeder W, Pelosi P, Koch E, Kuebler WM, Rossaint R, Kuhlen R (2009) Comparison of two in vivo microscopy techniques to visualize alveolar mechanics. J Clin Monit Comput 23:323–332

    Article  PubMed  Google Scholar 

  • Brazil TJ, Dagleish MP, McGorum BC, Dixon PM, Haslett C, Chilvers ER (2005) Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation. Clin Exp Allergy 35:854–865

    Article  CAS  PubMed  Google Scholar 

  • Carman CV, Springer TA (2004) A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 167:377–388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chavakis T, Athanasopoulos A, Rhee JS, Orlova V, Schmidt-Woll T, Bierhaus A, May AE, Celik I, Nawroth PP, Preissner KT (2005) Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment. Blood 105:1036–1043

    Article  CAS  PubMed  Google Scholar 

  • Cinamon G, Shinder V, Shamri R, Alon R (2004) Chemoattractant signals and β2 integrin occupancy at apical endothelial contacts combine with shear stress signals to promote transendothelial neutrophil migration. J Immunol 173:7282–7291

    Article  CAS  PubMed  Google Scholar 

  • Claesson-Welsh L, Welsh M, Ito N, Anand-Apte B, Soker S, Zetter B, O'Reilly M, Folkman J (1998) Angiostatin induces endothelial cell apoptosis and activation of focal adhesion kinase independently of the integrin-binding motif RGD. Proc Natl Acad Sci U S A 95:5579–5583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, DeVinney R, Doig CJ, Green FHY, Kubes P (2007) Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13:463–469

    Article  CAS  PubMed  Google Scholar 

  • Czermak BJ, Breckwoldt M, Ravage ZB, Huber-Lang M, Schmal H, Bless NM, Friedl HP, Ward PA (1999a) Mechanisms of enhanced lung injury during sepsis. Am J Pathol 154:1057–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, Schmal H, Friedl HP, Ward PA (1999b) Protective effects of C5a blockade in sepsis. Nat Med 5:788–792

    Article  CAS  PubMed  Google Scholar 

  • de Boer HC, Preissner KT, Bouma BN, de Groot PG (1995) Internalization of vitronectin-thrombin-antithrombin complex by endothelial cells leads to deposition of the complex into the subendothelial matrix. J Biol Chem 270:30733–30740

    Article  PubMed  Google Scholar 

  • Doerschuk CM (1999) Neutrophil rheology and transit through capillaries and sinusoids. Am J Respir Crit Care Med 159:1693–1695

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM (2001) Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 8:71–88

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM, Allard MF, Martin BA, MacKenzie A, Autor AP, Hogg JC (1987a) Marginated pool of neutrophils in rabbit lungs. J Appl Physiol 63:1806–1815

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM, Allard MF, Martin BA, MacKenzie A, Autor AP, Hogg JC (1987b) Marginated pool of neutrophils in rabbit lungs. J Appl Physiol (Bethesda, Md : 1985) 63:1806–1815

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM, Beyers N, Coxson HO, Wiggs B, Hogg JC (1993) Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung. J Appl Physiol (Bethesda, Md : 1985) 74:3040–3045

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM, Downey GP, Doherty DE, English D, Gie RP, Ohgami M, Worthen GS, Henson PM, Hogg JC (1990a) Leukocyte and platelet margination within microvasculature of rabbit lungs. J Appl Physiol 68:1956–1961

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM, Quinlan WM, Doyle NA, Bullard DC, Vestweber D, Jones ML, Takei F, Ward PA, Beaudet AL (1996) The role of P-selectin and ICAM-1 in acute lung injury as determined using blocking antibodies and mutant mice. J Immunol 157:4609–4614

    CAS  PubMed  Google Scholar 

  • Doerschuk CM, Tasaka S, Wang Q (2000) CD11/CD18-dependent and -independent neutrophil emigration in the lungs: how do neutrophils know which route to take? Am J Respir Cell Mol Biol 23:133–136

    Article  CAS  PubMed  Google Scholar 

  • Doerschuk CM, Winn RK, Coxson HO, Harlan JM (1990b) CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits. J Immunol (Baltimore, Md : 1950) 144:2327–2333

    CAS  PubMed  Google Scholar 

  • Falcone DJ, Khan KMF, Layne T, Fernandes L (1998) Macrophage formation of Angiostatin during inflammation, a byproduct of thje activation of plasminogen. J Biol Chem 273:31480–31485

  • Felding-Habermann B, Cheresh DA (1993) Vitronectin and its receptors. Curr Opin Cell Biol 5:864–868

    Article  CAS  PubMed  Google Scholar 

  • Francois PP, Preissner KT, Herrmann M, Haugland RP, Vaudaux P, Lew DP, Krause KH (1999) Vitronectin interaction with glycosaminoglycans. Kinetics, structural determinants, and role in binding to endothelial cells. J Biol Chem 274:37611–37619

    Article  CAS  PubMed  Google Scholar 

  • Gechtman Z, Belleli A, Lechpammer S, Shaltiel S (1997) The cluster of basic amino acids in vitronectin contributes to its binding of plasminogen activator inhibitor-1: evidence from thrombin-, elastase- and plasmin-cleaved vitronectins and anti-peptide antibodies. Biochem J 325(Pt 2):339–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geiger JH, Cnudde SE (2004) What the structure of angiostatin may tell us about its mechanism of action. J Thromb Haemost 2:23–34

    Article  CAS  PubMed  Google Scholar 

  • Grommes J, Alard JE, Drechsler M, Wantha S, Morgelin M, Kuebler WM, Jacobs M, von Hundelshausen P, Markart P, Wygrecka M, Preissner KT, Hackeng TM, Koenen RR, Weber C, Soehnlein O (2012) Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. Am J Respir Crit Care Med 185:628–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurpreet Kaur A, Anish M, George B, Sheldon W, Wolfgang MK, Baljit S, Dean C (2017) Physics in medicine and biology

  • Haslett C (1999) Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 160:5

    Article  Google Scholar 

  • Haslett C, Savill JS, Meagher L (1989) The neutrophil. Curr Opin Immunol 2:10–18

    Article  CAS  PubMed  Google Scholar 

  • Hatton MW, Day S, Southward SM, Dereske M, Ross B, Seidlitz E, Singh G, Richardson M (2001) Metabolism of rabbit angiostatin glycoforms I and II in rabbits: angiostatin-I leaves the intravascular space faster and appears to have greater anti-angiogenic activity than angiostatin-II. J Lab Clin Med 138:83–93

    Article  CAS  PubMed  Google Scholar 

  • Heemskerk N, Schimmel L, Oort C, van Rijssel J, Yin T, Ma B, van Unen J, Pitter B, Huveneers S, Goedhart J, Wu Y, Montanez E, Woodfin A, van Buul JD (2016) F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. Nat Commun 7:10493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heit B, Robbins SM, Downey CM, Guan Z, Colarusso P, Miller JB, Jirik FR, Kubes P (2008) PTEN functions to 'prioritize' chemotactic cues and prevent 'distraction' in migrating neutrophils. Nat Immunol 9:743–752

    Article  CAS  PubMed  Google Scholar 

  • Heit B, Tavener S, Raharjo E, Kubes P (2002) An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients. J Cell Biol 159:91–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hellewell PG, Young SK, Henson PM, Worthen GS (1994) Disparate role of the beta 2-integrin CD18 in the local accumulation of neutrophils in pulmonary and cutaneous inflammation in the rabbit. Am J Respir Cell Mol Biol 10:391–398

    Article  CAS  PubMed  Google Scholar 

  • Hoenderdos K, Condliffe A (2013) The neutrophil in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 48:531–539

    Article  CAS  PubMed  Google Scholar 

  • Hogg JC, Coxson HO, Brumwell ML, Beyers N, Doerschuk CM, MacNee W, Wiggs BR (1994) Erythrocyte and polymorphonuclear cell transit time and concentration in human pulmonary capillaries. J Appl Physiol (Bethesda, Md : 1985) 77:1795–1800

    Article  CAS  PubMed  Google Scholar 

  • Hogg JC, Doerschuk CM, Wiggs B, Minshall D (1992) Neutrophil retention during a single transit through the pulmonary circulation. J Appl Physiol 73:1683–1685

    Article  CAS  PubMed  Google Scholar 

  • Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, Lambris JD, Warner RL, Flierl MA, Hoesel LM, Gebhard F, Younger JG, Drouin SM, Wetsel RA, Ward PA (2006) Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 12:682–687

    Article  CAS  PubMed  Google Scholar 

  • Ibbotson GC, Doig C, Kaur J, Gill V, Ostrovsky L, Fairhead T, Kubes P (2001) Functional α4-integrin: a newly identified pathway of neutrophil recruitment in critically ill septic patients. Nat Med 7:465–470

    Article  CAS  PubMed  Google Scholar 

  • Ichimura H, Parthasarathi K, Lindert J, Bhattacharya J (2006) Lung surfactant secretion by interalveolar Ca2+ signaling. Am J Physiol Lung Cell Mol Physiol 291:L596–L601

    Article  CAS  PubMed  Google Scholar 

  • Janardhan KS, Appleyard GD, Singh B (2004) Expression of integrin subunits alphav and beta3 in acute lung inflammation. Histochem Cell Biol 121:383–390

    Article  CAS  PubMed  Google Scholar 

  • Janardhan KS, Charavaryamath C, Aulakh GK, Singh B (2012) Integrin beta 3 is not critical for neutrophil recruitment in a mouse model of pneumococcal pneumonia. Cell Tissue Res 348:177–187

    Article  CAS  PubMed  Google Scholar 

  • Jang YC, Tsou R, Gibran NS, Isik FF (2000) Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice. Surgery 127:696–704

    Article  CAS  PubMed  Google Scholar 

  • Jurasz P, Santos-Martinez MJ, Radomska A, Radomski MW (2006) Generation of platelet angiostatin mediated by urokinase plasminogen activator: effects on angiogenesis. J Thromb Haemost 4:1095–1106

    Article  CAS  PubMed  Google Scholar 

  • Kamei M, Carman CV (2010) New observations on the trafficking and diapedesis of monocytes. Curr Opin Hematol 17:43–52

    Article  PubMed  Google Scholar 

  • Kelly MM, McNagny K, Williams DL, van Rooijen N, Maxwell L, Gwozd C, Mody CH, Kubes P (2008) The lung responds to zymosan in a unique manner independent of toll-like receptors, complement, and dectin-1. Am J Respir Cell Mol Biol 38:227–238

    Article  CAS  PubMed  Google Scholar 

  • Khan AI, Heit B, Andonegui G, Colarusso P, Kubes P (2005) Lipopolysaccharide: a p38 MAPK-dependent disrupter of neutrophil chemotaxis. Microcirculation 12:421–432

    Article  CAS  PubMed  Google Scholar 

  • Klebanoff SJ, Kettle AJ, Rosen H, Winterbourn CC, Nauseef WM (2013) Myeloperoxidase: a front-line defender against phagocytosed microorganisms. J Leukoc Biol 93:185–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kost C, Benner K, Stockmann A, Linder D, Preissner KT (1996) Limited plasmin proteolysis of vitronectin. Characterization of the adhesion protein as morpho-regulatory and angiostatin-binding factor. Eur J Biochem 236:682–688

    Article  CAS  PubMed  Google Scholar 

  • Kost C, Stuber W, Ehrlich HJ, Pannekoek H, Preissner KT (1992) Mapping of binding sites for heparin, plasminogen activator inhibitor-1, and plasminogen to vitronectin's heparin-binding region reveals a novel vitronectin-dependent feedback mechanism for the control of plasmin formation. J Biol Chem 267:12098–12105

    CAS  PubMed  Google Scholar 

  • Kreisel D, Nava RG, Li W, Zinselmeyer BH, Wang B, Lai J, Pless R, Gelman AE, Krupnick AS, Miller MJ (2010) In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc Natl Acad Sci U S A 107:18073–18078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuebler WM, Parthasarathi K, Wang PM, Bhattacharya J (2000) A novel signaling mechanism between gas and blood compartments of the lung. J Clin Invest 105:905–913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamm WJ, Bernard SL, Wagner WW Jr, Glenny RW (2005) Intravital microscopic observations of 15-microm microspheres lodging in the pulmonary microcirculation. J Appl Physiol (Bethesda, Md : 1985) 98:2242–2248

    Article  PubMed  Google Scholar 

  • Lay AJ, Jiang XM, Kisker O, Flynn E, Underwood A, Condron R, Hogg PJ (2000) Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase. Nature 408:869–873

    Article  CAS  PubMed  Google Scholar 

  • Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689

    Article  CAS  PubMed  Google Scholar 

  • Li R, Ren M, Chen N, Luo M, Zhang Z, Wu J (2012) Vitronectin increases vascular permeability by promoting VE-cadherin internalization at cell junctions. PLoS ONE 7:e37195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Dong X, Wang Z, Liu W, Deng N, Ding Y, Tang L, Hla T, Zeng R, Li L, Wu D (2005) Regulation of PTEN by Rho small GTPases. Nat Cell Biol 2005:399–404

  • Lokuta MA, Huttenlocher A (2005) TNF-α promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway. J Leukoc Biol 78:210–219

    Article  CAS  PubMed  Google Scholar 

  • Looney MR, Bhattacharya J (2014) Live imaging of the lung. Annu Rev Physiol 76:431–445

    Article  CAS  PubMed  Google Scholar 

  • Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF (2011) Stabilized imaging of immune surveillance in the mouse lung. Nat Methods 8:91–96

    Article  CAS  PubMed  Google Scholar 

  • Ma AC, Kubes P (2008) Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemost 6:415–420

    Article  CAS  PubMed  Google Scholar 

  • Maus UA, Backi M, Winter C, Srivastava M, Schwarz MK, Rückle T, Paton JC, Briles D, Mack M, Welte T, Maus R, Bohle RM, Seeger W, Rommel C, Hirsch E, Lohmeyer J, Preissner KT (2007) Importance of phosphoinositide 3-kinase γ in the host defense against pneumococcal infection. Am J Respir Crit Care Med 175:958–966

    Article  CAS  PubMed  Google Scholar 

  • Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S (2000) Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med 28:451–457

    Article  CAS  PubMed  Google Scholar 

  • McDonald B, McAvoy EF, Lam F, Gill V, de la Motte C, Savani RC, Kubes P (2008) Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med 205:915–927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDonald B, Urrutia R, Yipp BG, Jenne CN, Kubes P (2012) Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell Host Microbe 12:324–333

    Article  CAS  PubMed  Google Scholar 

  • McDonald DM, Yao LC, Baluk P (2011) Dynamics of airway blood vessels and lymphatics: lessons from development and inflammation. Proc Am Thorac Soc 8:504–507

    Article  PubMed  PubMed Central  Google Scholar 

  • McEver RP (2015) Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res 107:331–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mertens M, Tabuchi A, Meissner S, Krueger A, Schirrmann K, Kertzscher U, Pries AR, Slutsky AS, Koch E, Kuebler WM (2009) Alveolar dynamics in acute lung injury: heterogeneous distension rather than cyclic opening and collapse. Crit Care Med 37:2604–2611

    Article  PubMed  Google Scholar 

  • Mihalache CC, Yousefi S, Conus S, Villiger PM, Schneider EM, Simon HU (2011) Inflammation-associated autophagy-related programmed necrotic death of human neutrophils characterized by organelle fusion events. J Immunol (Baltimore, Md : 1950) 186:6532–6542

    Article  CAS  PubMed  Google Scholar 

  • Milis L, Morris CA, Sheehan MC, Charlesworth JA, Pussell BA (1993) Vitronectin-mediated inhibition of complement: evidence for different binding sites for C5b-7 and C9. Clin Exp Immunol 92:114–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moser TL, Kenan DJ, Ashley TA, Roy JA, Goodman MD, Misra UK, Cheek DJ, Pizzo SV (2001) Endothelial cell surface F1-F0 ATP synthase is active in ATP synthesis and is inhibited by angiostatin. Proc Natl Acad Sci U S A 98:6656

  • Panetti TS, McKeown-Longo PJ (1993) Receptor-mediated endocytosis of vitronectin is regulated by its conformational state. J Biol Chem 268:11988–11993

    CAS  PubMed  Google Scholar 

  • Panetti TS, Wilcox SA, Horzempa C, McKeown-Longo PJ (1995) Alpha v beta 5 integrin receptor-mediated endocytosis of vitronectin is protein kinase C-dependent. J Biol Chem 270:18593–18597

    Article  CAS  PubMed  Google Scholar 

  • Park SY, Shrestha S, Youn YJ, Kim JK, Kim SY, Kim HJ, Park SH, Ahn WG, Kim S, Lee MG, Jung KS, Park YB, Mo EK, Ko Y, Lee SY, Koh Y, Park MJ, Song DK, Hong CW (2017) Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation During Sepsis. Am J Respir Crit Care Med

  • Parker LC, Whyte MK, Dower SK, Sabroe I (2005) The expression and roles of toll-like receptors in the biology of the human neutrophil. J Leukoc Biol 77:886–892

    Article  CAS  PubMed  Google Scholar 

  • Perlman CE, Lederer DJ, Bhattacharya J (2011) Micromechanics of alveolar edema. Am J Respir Cell Mol Biol 44:34–39

    Article  CAS  PubMed  Google Scholar 

  • Petri B, Kaur J, Long EM, Li H, Parsons SA, Butz S, Phillipson M, Vestweber D, Patel KD, Robbins SM, Kubes P (2011) Endothelial LSP1 is involved in endothelial dome formation, minimizing vascular permeability changes during neutrophil transmigration in vivo. Blood 117:942–952

    Article  CAS  PubMed  Google Scholar 

  • Phillipson M, Kaur J, Colarusso P, Ballantyne CM, Kubes P (2008) Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration. PLoS ONE 3:e1649

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Piccard H, Van den Steen PE, Opdenakker G (2007) Hemopexin domains as multifunctional liganding modules in matrix metalloproteinases and other proteins. J Leukoc Biol 81:870–892

    Article  CAS  PubMed  Google Scholar 

  • Podack ER, Muller-Eberhard HJ (1979) Isolation of human S-protein, an inhibitor of the membrane attack complex of complement. J Biol Chem 254:9808–9814

    CAS  PubMed  Google Scholar 

  • Podor TJ, Campbell S, Chindemi P, Foulon DM, Farrell DH, Walton PD, Weitz JI, Peterson CB (2002) Incorporation of vitronectin into fibrin clots. Evidence for a binding interaction between vitronectin and gamma a/gamma' fibrinogen. J Biol Chem 277:7520–7528

    Article  CAS  PubMed  Google Scholar 

  • Preissner KT (1991) Structure and biological role of vitronectin. Annu Rev Cell Biol 7:275–310

    Article  CAS  PubMed  Google Scholar 

  • Preissner KT, Seiffert D (1998) Role of vitronectin and its receptors in haemostasis and vascular remodeling. Thromb Res 89:1–21

    Article  CAS  PubMed  Google Scholar 

  • Ratliff NB, Wilson JW, Mikat E, Hackel DB, Graham TC (1971) The lung in hemorrhagic shock. IV. The role of neutrophilic polymorphonuclear leukocytes. Am J Pathol 65:325–334

    CAS  PubMed  PubMed Central  Google Scholar 

  • Riethmuller C, Nasdala I, Vestweber D (2008) Nano-surgery at the leukocyte-endothelial docking site. Pflugers Arch Eur J Physiol 456:71–81

    Article  CAS  Google Scholar 

  • Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, Zetoune FS, Gerard NP, Cianflone K, Köhl J, Gerard C, Sarma JV, Ward PA (2008) Functional roles for C5a receptors in sepsis. Nat Med 14:551–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogers DE, Melly MA (1957) Studies on bacteriemia. II. Further observations on the granulocytopenia induced by the intravenous injection of staphylococci. J Exp Med 105:99–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosen H (2013) Editorial: of mice and men--yet again. J Leukoc Biol 94:210–212

    Article  CAS  PubMed  Google Scholar 

  • Salazar-Pelaez LM, Abraham T, Herrera AM, Correa MA, Ortega JE, Pare PD, Seow CY (2015) Vitronectin expression in the airways of subjects with asthma and chronic obstructive pulmonary disease. PLoS ONE 10:e0119717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Salek-Ardakani S, Arrand JR, Shaw D, Mackett M (2000) Heparin and heparan sulfate bind interleukin-10 and modulate its activity. Blood 96:1879–1888

    CAS  PubMed  Google Scholar 

  • Scapini P, Nesi L, Morini M, Tanghetti E, Belleri M, Noonan D, Presta M, Albini A, Cassatella MA (2002) Generation of biologically active Angiostatin Kringle 1-3 by activated human neutrophils 1. J Immunol 168:5798–5804

    Article  CAS  PubMed  Google Scholar 

  • Schenkel AR, Mamdouh Z, Muller WA (2004) Locomotion of monocytes on endothelium is a critical step during extravasation. Nat Immunol 5:393–400

    Article  CAS  PubMed  Google Scholar 

  • Schousboe SL, Egelund R, Kirkegaard T, Preissner KT, Rodenburg KW, Andreasen PA (2000) Vitronectin and substitution of a beta-strand 5A lysine residue potentiate activity-neutralization of PA inhibitor-1 by monoclonal antibodies against alpha-helix F. Thromb Haemost 83:742–751

    CAS  PubMed  Google Scholar 

  • Schulte D, Küppers V, Dartsch N, Broermann A, Li H, Zarbock A, Kamenyeva O, Kiefer F, Khandoga A, Massberg S, Vestweber D (2011) Stabilizing the VE-cadherin–catenin complex blocks leukocyte extravasation and vascular permeability. EMBO J 30:4157–4170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schvartz I, Seger D, Shaltiel S (1999) Vitronectin. Int J Biochem Cell Biol 31:539–544

    Article  CAS  PubMed  Google Scholar 

  • Seiffert D (1997) Constitutive and regulated expression of vitronectin. Histol Histopathol 12:787–797

    CAS  PubMed  Google Scholar 

  • Seiffert D, Loskutoff DJ (1996) Type 1 plasminogen activator inhibitor induces multimerization of plasma vitronectin. A suggested mechanism for the generation of the tissue form of vitronectin in vivo. J Biol Chem 271:29644–29651

    Article  CAS  PubMed  Google Scholar 

  • Seiffert D, Schleef RR (1996) Two functionally distinct pools of vitronectin (Vn) in the blood circulation: identification of a heparin-binding competent population of Vn within platelet alpha-granules. Blood 88:552–560

    CAS  PubMed  Google Scholar 

  • Sheehan M, Morris CA, Pussell BA, Charlesworth JA (1995) Complement inhibition by human vitronectin involves non-heparin binding domains. Clin Exp Immunol 101:136–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh B, Fu C, Bhattacharya J (2000) Vascular expression of the αvβ3-integrin in lung and other organs. Am J Phys Lung Cell Mol Phys 278:217–226

    Google Scholar 

  • Singh B, Janardhan KS, Kanthan R (2005) Expression of angiostatin, integrin αvβ3, and vitronectin in human lungs in sepsis. Exp Lung Res 31:771–782

    Article  CAS  PubMed  Google Scholar 

  • Smith MR, Wood WB (1947) Studies on the mechanism of Recovery in pneumonia due to FRIEDLADER'S bacillus : iii. The role of "surface phagocytosis" in the destruction of the microorganisms in the lung. J Exp Med 86:257–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Standker L, Enger A, Schulz-Knappe P, Wohn KD, Germer M, Raida M, Forssmann WG, Preissner KT (1996) Structural and functional characterization of vitronectin-derived RGD-containing peptides from human hemofiltrate. Eur J Biochem 241:557–563

    Article  CAS  PubMed  Google Scholar 

  • Stockmann A, Hess S, Declerck P, Timpl R, Preissner KT (1993) Multimeric vitronectin. Identification and characterization of conformation-dependent self-association of the adhesive protein. J Biol Chem 268:22874–22882

    CAS  PubMed  Google Scholar 

  • Stohlawetz P, Folman CC, Von Dem Borne AEK, Pernerstorfer T, Eichler HG, Panzer S, Jilma B (1999) Effects of endotoxemia on thrombopoiesis in men. Thromb Haemost 81:613–617

    CAS  PubMed  Google Scholar 

  • Suresh K, Shimoda LA (2016) Lung circulation. Compr Phys 6:897–943

    Article  Google Scholar 

  • Suri SS, Mills S, Aulakh GK, Rakotondradany F, Fenniri H, Singh B (2011) RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation. Int J Nanomedicine 6:3113–3123

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tabuchi A, Mertens M, Kuppe H, Pries AR, Kuebler WM (2008) Intravital microscopy of the murine pulmonary microcirculation. J Appl Physiol (Bethesda, Md : 1985) 104:338–346

    Article  PubMed  Google Scholar 

  • Tabuchi A, Styp-Rekowska B, Slutsky AS, Wagner PD, Pries AR, Kuebler WM (2013) Precapillary oxygenation contributes relevantly to gas exchange in the intact lung. Am J Respir Crit Care Med 188:474–481

    Article  PubMed  Google Scholar 

  • Tarui T, Majumdar M, Miles LA, Ruf W, Takada Y (2002) Plasmin-induced migration of endothelial cells: a potential target for the anti-angiogenic action of angiostatin. J Biol Chem 277:33564–33570

    Article  CAS  PubMed  Google Scholar 

  • Tasaka S, Richer SE, Mizgerd JP, Doerschuk CM (2002) Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice. Am J Respir Crit Care Med 166:53–60

    Article  PubMed  Google Scholar 

  • Terry RJ (1939) A thoracic window for observation of the lung in a living Animal. Science 90:43–44

    Article  CAS  PubMed  Google Scholar 

  • Thanabalasuriar A, Neupane AS, Wang J, Krummel MF, Kubes P (2016) iNKT cell emigration out of the lung vasculature requires neutrophils and monocyte-derived dendritic cells in inflammation. Cell Rep 16:3260–3272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thanabalasuriar A, Surewaard BG, Willson ME, Neupane AS, Stover CK, Warrener P, Wilson G, Keller AE, Sellman BR, DiGiandomenico A, Kubes P (2017) Bispecific antibody targets multiple Pseudomonas Aeruginosa evasion mechanisms in the lung vasculature. J Clin Invest 127:2249–2261

    Article  PubMed  PubMed Central  Google Scholar 

  • Tolosano E, Altruda F (2002) Hemopexin: structure, function, and regulation. DNA Cell Biol 21:297–306

    Article  CAS  PubMed  Google Scholar 

  • Troyanovsky B, Levchenko T, Mansson G, Matvijenko O, Holmgren L (2001) Angiomotin an Angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol 152:1247–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsokos M (2003) Immunohistochemical detection of sepsis-induced lung injury in human autopsy material. Legal Med 5:73–86

    Article  CAS  PubMed  Google Scholar 

  • Tsukada H, Ying X, Fu C, Ishikawa S, McKeown-Longo P, Albelda S, Bhattacharya S, Bray BA, Bhattacharya J (1995) Ligation of endothelial alpha v beta 3 integrin increases capillary hydraulic conductivity of rat lung. Circ Res 77:651–659

    Article  CAS  PubMed  Google Scholar 

  • Tsuruta Y, Park YJ, Siegal GP, Liu G, Abraham E (2007) Involvement of vitronectin in lipopolysaccaride-induced acute lung injury. J Immunol (Baltimore, Md : 1950) 179:7079–7086

    Article  CAS  PubMed  Google Scholar 

  • Vestweber D (2012) Relevance of endothelial junctions in leukocyte extravasation and vascular permeability. Ann N Y Acad Sci 1257:184–192

    Article  CAS  PubMed  Google Scholar 

  • Vestweber D (2015) How leukocytes cross the vascular endothelium. Nat Rev Immunol 15:692–704

    Article  CAS  PubMed  Google Scholar 

  • Wagner JG, Roth RA (2000) Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol Rev 52:349–374

    CAS  PubMed  Google Scholar 

  • Wagner WW Jr (1969) Pulmonary microcirculatory observations in vivo under physiological conditions. J Appl Physiol 26:375–377

    Article  PubMed  Google Scholar 

  • Wagner WW Jr, Latham LP, Gillespie MN, Guenther JP, Capen RL (1982) Direct measurement of pulmonary capillary transit times. Science 218:379–381

    Article  PubMed  Google Scholar 

  • Wang MJ, Artemenko Y, Cai WJ, Iglesias PA, Devreotes PN (2014) The directional response of chemotactic cells depends on a balance between cytoskeletal architecture and the external gradient. Cell Rep 9:1110–1121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warren BA, de Bono AH (1969) The ultrastructure of early rejection phenomena in lung homografts in dogs. Br J Exp Pathol 50:593–599

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weibel ER (2009) What makes a good lung? Swiss Med Wkly 139:375–386

    PubMed  Google Scholar 

  • Wiggs BR, English D, Quinlan WM, Doyle NA, Hogg JC, Doerschuk CM (1994) Contributions of capillary pathway size and neutrophil deformability to neutrophil transit through rabbit lungs. J Appl Physiol (Bethesda, Md : 1985) 77:463–470

    Article  CAS  PubMed  Google Scholar 

  • Wilson C, Saunter CD, Girkin JM, McCarron JG (2016) Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium. FASEB J 30:2000–2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Windsor AC, Walsh CJ, Mullen PG, Cook DJ, Fisher BJ, Blocher CR, Leeper-Woodford SK, Sugerman HJ, Fowler AA 3rd (1993) Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation. J Clin Invest 91:1459–1468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong CH, Jenne CN, Lee WY, Leger C, Kubes P (2011) Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science 334:101–105

    Article  CAS  PubMed  Google Scholar 

  • Wood WB Jr, Smith MR, Perry WD, Berry JW (1951) Studies on the cellular immunology of acute bacteremia. I. Intravascular leucocytic reaction and surface phagocytosis. J Exp Med 94:521–534

    Article  PubMed  PubMed Central  Google Scholar 

  • Wood WB Jr, Smith MR, Watson B (1946) Surface phagocytosis--its relation to the mechanism of Recovery in pneumococcal pneumonia. Science 104:28–29

    Article  Google Scholar 

  • Yao L, Yago T, Shao B, Liu Z, Silasi-Mansat R, Setiadi H, Lupu F, McEver RP (2013) Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice. Blood 122:3832–3842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao LC, McDonald DM (2014) Plasticity of airway lymphatics in development and disease. Adv Anat Embryol Cell Biol 214:41–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Ying X, Minamiya Y, Fu C, Bhattacharya J (1996) Ca2+ waves in lung capillary endothelium. Circ Res 79:898–908

    Article  CAS  PubMed  Google Scholar 

  • Yipp BG, Andonegui G, Howlett CJ, Robbins SM, Hartung T, Ho M, Kubes P (2002) Profound differences in leukocyte-endothelial cell responses to lipopolysaccharide versus lipoteichoic acid. J Immunol 168:4650–4658

    Article  CAS  PubMed  Google Scholar 

  • Yipp BG, Kim JH, Lima R, Zbytnuik LD, Petri B, Swanlund N, Ho M, Szeto VG, Tak T, Koenderman L, Pickkers P, Tool ATJ, Kuijpers TW, van den Berg TK, Looney MR, Krummel MF, Kubes P (2017) The lung is a host defense Niche for immediate Neutrophil-Mediated vascular protection. Sci Immunol 2

  • Yipp BG, Kubes P (2013) NETosis: how vital is it? Blood 122:2784–2794

    Article  CAS  PubMed  Google Scholar 

  • Zanetti A, Conforti G, Hess S, Martin-Padura I, Ghibaudi E, Preissner KT, Dejana E (1994) Clustering of vitronectin and RGD peptides on microspheres leads to engagement of integrins on the luminal aspect of endothelial cell membrane. Blood 84:1116–1123

    CAS  PubMed  Google Scholar 

  • Zheng X, Saunders TL, Camper SA, Samuelson LC, Ginsburg D (1995) Vitronectin is not essential for normal mammalian development and fertility. Proc Natl Acad Sci U S A 92:12426–12430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I would like to acknowledge that the images shown in this article were part of research work carried out during my doctoral and post-doctoral fellowships: CIHR-THRUST as well as Eyes High Postdoctoral Scholarship carried out at the Canadian Light Source (University of Saskatchewan) and Live Cell Imaging Core (University of Calgary), respectively. Funding for these projects was obtained from the Natural Sciences and Engineering Research Council of Canada (NSERC) and Canadian Institutes of Health Research (CIHR).

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  1. Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada

    Gurpreet Kaur Aulakh

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Aulakh, G.K. Neutrophils in the lung: “the first responders”. Cell Tissue Res 371, 577–588 (2018). https://doi.org/10.1007/s00441-017-2748-z

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